SpasticityPhase 3NCT00711646
A Study of Sativex® for Relief of Spasticity in Subjects With Multiple Sclerosis.
A Phase 3 study testing Sativex® in people with Spasticity and Multiple Sclerosis, run by Jazz Pharmaceuticals at 1 site in United Kingdom.
Trial summary
The purpose of this study is to evaluate the efficacy, safety and tolerability of Sativex® in subjects diagnosed with MS and spasticity. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Spasticity, Multiple Sclerosis
- What is being tested?
- Sativex®
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 189 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jun 2002to Mar 2004
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to give informed consent.
- Male or female, aged 18 years or above.
- Stable disease for at least three months prior to study entry, in the opinion of the investigator.
- Diagnosed with MS whose spasticity was not wholly relieved with the therapy at the time of study entry.
- Significant spasticity in at least two muscle groups defined as a score of two or more on the Ashworth Scale for each muscle group.
- Stable dose of current anti-spasticity medication for at least 30 days prior to study entry.
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- Willing to maintain a stable dose of anti-spasticity medication and level of physiotherapy for the duration of the study.
- Clinically acceptable laboratory results at Visit 2.
- Willing, if female and of child bearing potential or male subjects with a partner of child bearing potential, to ensure that effective contraception was used during the study and for three months thereafter.
- No cannabinoid use (cannabis, Marinol® or Nabilone) for at least seven days before Visit 1 and were willing to abstain from any use of cannabis during the study.
- Able (in the investigators opinion) and willing to comply with all study requirements.
- Willing for the Home Office to be notified of his or her participation in the study (applicable to the UK centres only).
- Willing to allow his or her GP and consultant, if appropriate, to be notified of participation in the study.
Who cannot join
- History of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
- Known history of alcohol or substance abuse.
- Severe cardiovascular disorder, such as ischaemic heart disease, arrhythmias, poorly controlled hypertension or severe heart failure.
- History of epilepsy.
- Female subject who was pregnant, lactating or planning pregnancy during the course of the study.
- Significant renal or hepatic impairment.
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- Scheduled elective surgery or other procedures requiring general anaesthesia during the study.
- Subject who was terminally ill or was inappropriate for placebo medication.
- Any other significant disease or disorder which, in the opinion of the investigator, either put the subject at risk because of participation in the study, or influenced the result of the study, or the subject's ability to participate in the study.
- Regular levodopa (Sinemet®, Sinemet Plus®, Levodopa, L-dopa, Madopar®, Benserazide) therapy within seven days of study entry.
- Male subject receiving sildenafil (Viagra®) and unwilling to stop medication for the duration of the study.
- Subjects who were taking fentanyl (Durogesic®, Actiq®)
- Subjects who were taking antiarrhythmic medications.
- Known or suspected hypersensitivity to cannabinoids or any of the excipients of the study medications.
- Known or suspected adverse reaction to cannabinoids.
- Planned travel outside the UK during the study (applicable to the UK centres only).
- Donation of blood during the study.
- Subjects who had participated in another research study in the 12 weeks prior to study entry.
- Subjects previously randomised into this study.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Royal Berkshire Hospital
Reading, Oxfordshire, RG1 5AN
About this study
Official title: A Double Blind, Randomised, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of Cannabis Based Medicine 1:1 THC:CBD Compared With Placebo for the Treatment of Spasticity in Patients With Multiple Sclerosis.
The purpose of this study is to evaluate the efficacy, safety and tolerability of Sativex® in subjects diagnosed with MS and spasticity.
Read the detailed description
This was an eight week (two weeks baseline, six weeks treatment), multicentre, double blind, randomised, placebo controlled parallel group study to evaluate the efficacy, safety and tolerability of Sativex® in subjects diagnosed with MS and spasticity. Subjects were screened to determine eligibility and completed a two week baseline period. Subjects then returned to the site for assessment, randomisation and dose introduction. Visits occurred at the end of treatment week two and at the end of the study (treatment week six) or withdrawal.
- Conditions
- Spasticity, Multiple Sclerosis
- Being tested
- Sativex®, Placebo
- Keywords
- Spasticity, Multiple Sclerosis
- Medical subject headings
- Muscle Spasticity, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sativex®Drug
Also called GW-1000-02
containing THC (27 mg/ml):CBD (25 mg/ml), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring. Maximum permitted dose was eight actuations in any three hour period and 24 actuations (THC 65 mg: CBD 60 mg) in 24 hours
PlaceboDrug
Also called GW-4001-01
containing peppermint oil, 0.05% (v/v), quinoline yellow, 0.005% (w/v), sunset yellow, 0.0025% (w/v), in ethanol:propylene glycol (50:50) excipient.
| Study group | Role | What they receive |
|---|---|---|
| Sativex | Experimental | Not described Receives: Drug: Sativex® |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of Change From Baseline in the Mean Spasticity 0-10 Numerical Rating Scale Score.
The spasticity Numerical Rating Scale was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your average spasticity in the last 24 hours" where 0 = no spasticity and 10 = worst ever spasticity. For the analysis, end of treatment was defined as the mean of the last seven days in the study or the last three days if the subject withdrew due to worsening spasticity or lack of efficacy. A negative value indicates an improvement in spasticity score from baseline.
Measured: 0-52 days
Secondary outcomes (6)
Change From Baseline in Mean Ashworth Scale Score at the End of Treatment
The mean Ashworth Scale score across muscle groups was calculated using only those muscle groups with a score of greater than or equal to two at baseline. All 20 muscle groups were assessed for spasticity (using a 1-5 scale): 1= no increase in muscle tone to 5= passive movement is difficult and affected part is rigid in flexion or extension. The score for all 20 muscle groups were added to give a total score out of 100; minimum score was 20. A decrease in score indicates an improvement in condition.
Measured: Days 0 - 52
Change From Baseline in Mean Spasm Frequency Score at the End of Treatment
Each day subjects recorded in their diary the frequency of their spasms using the following scoring system: 0 = no spasms, 1 = one or fewer spasms per day, 2 = between one and five spasms per day, 3 = six to nine spasms per day, 4 = ten or more spasms per day or continuous contraction. For the analysis, end of treatment was defined as the mean of the last seven days in the study or the last three days if the subject withdrew due to worsening spasticity or lack of efficacy.
Measured: Days 0 - 52
Change From Baseline in Mean Motricity Index Score for the Arms
Arm - 3 movements were pinch grip, elbow flexion and shoulder abduction. The total arm score was the addition of the score for the 3 arm movements. One point was then added to give a maximum score of 100; minimum was 1 point. Where both arms were assessed, the average of the two limbs scores was used as the assessment score; otherwise the affected limb total score was used. An increase in score indicates an improvement in condition..
Measured: Day 7 and 52
Patient's Global Impression of Change in Condition at the End of Treatment
A 7-point Likert-type scale was used, with the question: 'Please assess the change in your condition since entry into the study using the scale below' with the markers "very much improved, much improved, slightly improved, no change, slightly worse, much worse or very much worse". At Visit 2 (Baseline) patients wrote a brief description of their condition which was used at end of treatment to aid their memory regarding their symptoms at study start. For each of above markers the number of participants were reported.
Measured: Day 52
Incidence of Adverse Events as a Measure of Subject Safety
The number of subjects who reported an adverse event during the course of the study is presented.
Measured: Day 0-52
Change From Baseline in Mean Motricity Index Score for the Legs
Ankle dorsiflexion, knee extension and hip flexion were assessed and scored to give a maximum of 100%. The Motricity Index score (scale 1-100) was recorded for limbs that had an associated Ashworth Scale score, which was greater than or equal to two at baseline.
Measured: Day 7 and Day 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2008 (estimated)
- Study startJun 2002
- Primary completionMar 2004
- Study completionMar 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for SpasticityStudies of the same condition, open and under way.
- More trials run by Jazz PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 189 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jazz Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Christine Collin, MB BS MRCP FRCP, Principal investigator, Royal Berkshire Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00711646
- Sponsor's protocol ID
- GWMS0106
- Status last verified
- Apr 2023
- First submitted
- 8 Jul 2008
- Last updated
- 6 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Collin C, Davies P, Mutiboko IK, Ratcliffe S; Sativex Spasticity in MS Study Group. Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis. Eur J Neurol. 2007 Mar;14(3):290-6. doi: 10.1111/j.1468-1331.2006.01639.x.
PubMed 17355549Di Marzo V, Centonze D. Placebo effects in a multiple sclerosis spasticity enriched clinical trial with the oromucosal cannabinoid spray (THC/CBD): dimension and possible causes. CNS Neurosci Ther. 2015 Mar;21(3):215-21. doi: 10.1111/cns.12358. Epub 2014 Dec 4.
PubMed 25475413
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double Blind, Randomised, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of Cannabis Based Medicine 1:1 THC:CBD Compared With Placebo for the Treatment of Spasticity in Patients With Multiple Sclerosis.
- ClinicalTrials.gov ID
- NCT00711646
- Acronym / sponsor ID
- GWMS0106
- Conditions
- Spasticity, Multiple Sclerosis
- Keywords
- Spasticity, Multiple Sclerosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 189 participants (actual)
- Lead sponsor
- Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jun 2002
- Primary completion
- Mar 2004 (actual)
- Study completion
- Mar 2004 (actual)
- First posted
- 9 Jul 2008 (estimated)
- Results
- Posted 14 Sep 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy, safety and tolerability of Sativex® in subjects diagnosed with MS and spasticity.
Detailed description
This was an eight week (two weeks baseline, six weeks treatment), multicentre, double blind, randomised, placebo controlled parallel group study to evaluate the efficacy, safety and tolerability of Sativex® in subjects diagnosed with MS and spasticity. Subjects were screened to determine eligibility and completed a two week baseline period. Subjects then returned to the site for assessment, randomisation and dose introduction. Visits occurred at the end of treatment week two and at the end of the study (treatment week six) or withdrawal.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sativex | Experimental | Drug: Sativex® |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Willing and able to give informed consent.
- Male or female, aged 18 years or above.
- Stable disease for at least three months prior to study entry, in the opinion of the investigator.
- Diagnosed with MS whose spasticity was not wholly relieved with the therapy at the time of study entry.
- Significant spasticity in at least two muscle groups defined as a score of two or more on the Ashworth Scale for each muscle group.
Key exclusion criteria (19 listed)
- History of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
- Known history of alcohol or substance abuse.
- Severe cardiovascular disorder, such as ischaemic heart disease, arrhythmias, poorly controlled hypertension or severe heart failure.
- History of epilepsy.
- Female subject who was pregnant, lactating or planning pregnancy during the course of the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sativex®Also: GW-1000-02containing THC (27 mg/ml):CBD (25 mg/ml), in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring. Maximum permitted dose was eight actuations in any three hour period and 24 actuations (THC 65 mg: CBD 60 mg) in 24 hours | Drug | Sativex |
| PlaceboAlso: GW-4001-01containing peppermint oil, 0.05% (v/v), quinoline yellow, 0.005% (w/v), sunset yellow, 0.0025% (w/v), in ethanol:propylene glycol (50:50) excipient. | Drug | Placebo |
Primary outcome
Assessment of Change From Baseline in the Mean Spasticity 0-10 Numerical Rating Scale Score.
Time frame: 0-52 days
The spasticity Numerical Rating Scale was completed at the same time each day, i.e. bedtime in the evening. The patient was asked "on a scale of '0 to 10', please indicate the number that best describes your average spasticity in the last 24 hours" where 0 = no spasticity and 10 = worst ever spasticity. For the analysis, end of treatment was defined as the mean of the last seven days in the study or the last three days if the subject withdrew due to worsening spasticity or lack of efficacy. A negative value indicates an improvement in spasticity score from baseline.
6 secondary outcomes
Change From Baseline in Mean Ashworth Scale Score at the End of Treatment
Time frame: Days 0 - 52
Change From Baseline in Mean Spasm Frequency Score at the End of Treatment
Time frame: Days 0 - 52
Change From Baseline in Mean Motricity Index Score for the Arms
Time frame: Day 7 and 52
Patient's Global Impression of Change in Condition at the End of Treatment
Time frame: Day 52
Incidence of Adverse Events as a Measure of Subject Safety
Time frame: Day 0-52
Change From Baseline in Mean Motricity Index Score for the Legs
Time frame: Day 7 and Day 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 17355549Collin C, Davies P, Mutiboko IK, Ratcliffe S; Sativex Spasticity in MS Study Group. Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis. Eur J Neurol. 2007 Mar;14(3):290-6. doi: 10.1111/j.1468-1331.2006.01639.x.
- Derived from this study: PubMed 25475413Di Marzo V, Centonze D. Placebo effects in a multiple sclerosis spasticity enriched clinical trial with the oromucosal cannabinoid spray (THC/CBD): dimension and possible causes. CNS Neurosci Ther. 2015 Mar;21(3):215-21. doi: 10.1111/cns.12358. Epub 2014 Dec 4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christine Collin, MB BS MRCP FRCP principal investigator
Royal Berkshire Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sativex® in people with Spasticity and Multiple Sclerosis, run by Jazz Pharmaceuticals at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Sep 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of Change From Baseline in the Mean Spasticity 0-10 Numerical Rating Scale Score. (time frame: 0-52 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00711646, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2023.